Because of their unique size-dependent optical, electronic, magnetic, and chemical properties, inorganic nanocrystals are becoming a new class of powerful tools in biological and medical applications for sensing, labeling, optical imaging, magnetic resonance imaging, cell separation, and treatment of disease. These applications require nanocrystals that are soluble and stable in aqueous solutions. To achieve water soluble and stable nanocrystals, nanocrystal coatings are needed because high-quality nanocrystals are generally synthesized in organic solutions and stabilized by hydrophobic ligands.
Presently, two general approaches have been developed for the coatings of hydrophobic nanocrystals with organic ligands to render them hydrophilic. The first approach is based on coordinate bonding. Functional groups (such as thiol, dithiol, phosphine and dopamine) are used to directly link hydrophilic groups onto the surface of hydrophobic nanocrystals, and displacing the hydrophobic ligands. The second approach uses hydrophobic van der Waals interactions between the hydrophobic ligands of the nanocrystals as prepared and hydrophobic tails of amphiphilic ligands, where the hydrophobic ligands on the nanocrystals are not displaced, and forming nanocrystal-micelles.
Unfortunately, water-soluble nanocrystals made by these two approaches often suffer from low stability and/or display high non-specific binding with non-target biomolecules. Water-soluble nanocrystals coated with PEGylated amphiphilic polymers have been shown to have very high stability and low nonspecific-absorption levels. Unfortunately, PEGylated polymer shells typically suffer from large hydrodynamic diameters (HDs) on the order of 30-40 nm, which can limit their use in applications such as in vivo cell imaging.
Therefore, the goal remains to develop stable water soluble nanocrystals which do not suffer from non-specific binding and have small hydrodynamic diameters. It also remains a goal to form water soluble nanocrystals that can be bound to an antibody or other biomolecules to allow specific interactions with specific biomolecules.